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The article focuses on the systemic insecticide fipronil and those which belong to the neonicotinoid family. The increasing global dependance on the prophylactic use of these potent neurotoxic systemic insecticides has raised concerns about their effects on biodiversity and ecosystem services provided by a wide range of affected species and environments.

Since their discovery in the late 1980s, neonicotinoid pesticides have become the most widely used class of insecticides worldwide, with large-scale applications ranging from plant protection (crops, vegetables, fruits), veterinary products, and biocides to invertebrate pest control in fish farming. In this review, we address the phenyl-pyrazole fipronil together with neonicotinoids because of similarities in their toxicity, physicochemical profiles, and presence in the environment. Neonicotinoids and fipronil currently account for approximately one third of the world insecticide market; the annual world production of the archetype neonicotinoid, imidacloprid, was estimated to be ca. 20,000 tonnes active substance in 2010. There were several reasons for the initial success of neonicotinoids and fipronil: (1) there was no known pesticide resistance in target pests, mainly because of their recent development, (2) their physicochemical properties included many advantages over previous generations of insecticides (i.e., organophosphates, carbamates, pyrethroids, etc.), and (3) they shared an assumed reduced operator and consumer risk. Due to their systemic nature, they are taken up by the roots or leaves and translocated to all parts of the plant, which, in turn, makes them effectively toxic to herbivorous insects. The toxicity persists for a variable period of time-depending on the plant, its growth stage, and the amount of pesticide applied. A wide variety of applications are available, including the most common prophylactic non-Good Agricultural Practices (GAP) application by seed coating. As a result of their extensive use and physicochemical properties, these substances can be found in all environmental compartments including soil, water, and air. Neonicotinoids and fipronil operate by disrupting neural transmission in the central nervous system of invertebrates. Neonicotinoids mimic the action of neurotransmitters, while fipronil inhibits neuronal receptors. In doing so, they continuously stimulate neurons leading ultimately to death of target invertebrates. Like virtually all insecticides, they can also have lethal and sublethal impacts on non-target organisms, including insect predators and vertebrates. Furthermore, a range of synergistic effects with other stressors have been documented. Here, we review extensively their metabolic pathways, showing how they form both compound-specific and common metabolites which can themselves be toxic. These may result in prolonged toxicity. Considering their wide commercial expansion, mode of action, the systemic properties in plants, persistence and environmental fate, coupled with limited information about the toxicity profiles of these compounds and their metabolites, neonicotinoids and fipronil may entail significant risks to the environment. A global evaluation of the potential collateral effects of their use is therefore timely. The present paper and subsequent chapters in this review of the global literature explore these risks and show a growing body of evidence that persistent, low concentrations of these insecticides pose serious risks of undesirable environmental impacts. [ABSTRACT FROM AUTHOR]

We assessed the state of knowledge regarding the effects of large-scale pollution with neonicotinoid insecticides and fipronil on non-target invertebrate species of terrestrial, freshwater and marine environments. A large section of the assessment is dedicated to the state of knowledge on sublethal effects on honeybees ( Apis mellifera) because this important pollinator is the most studied non-target invertebrate species. Lepidoptera (butterflies and moths), Lumbricidae (earthworms), Apoidae sensu lato (bumblebees, solitary bees) and the section 'other invertebrates' review available studies on the other terrestrial species. The sections on freshwater and marine species are rather short as little is known so far about the impact of neonicotinoid insecticides and fipronil on the diverse invertebrate fauna of these widely exposed habitats. For terrestrial and aquatic invertebrate species, the known effects of neonicotinoid pesticides and fipronil are described ranging from organismal toxicology and behavioural effects to population-level effects. For earthworms, freshwater and marine species, the relation of findings to regulatory risk assessment is described. Neonicotinoid insecticides exhibit very high toxicity to a wide range of invertebrates, particularly insects, and field-realistic exposure is likely to result in both lethal and a broad range of important sublethal impacts. There is a major knowledge gap regarding impacts on the grand majority of invertebrates, many of which perform essential roles enabling healthy ecosystem functioning. The data on the few non-target species on which field tests have been performed are limited by major flaws in the outdated test protocols. Despite large knowledge gaps and uncertainties, enough knowledge exists to conclude that existing levels of pollution with neonicotinoids and fipronil resulting from presently authorized uses frequently exceed the lowest observed adverse effect concentrations and are thus likely to have large-scale and wide ranging negative biological and ecological impacts on a wide range of non-target invertebrates in terrestrial, aquatic, marine and benthic habitats. [ABSTRACT FROM AUTHOR]

This article reports the findings of a survey developed to assess the current use of antifungal prophylaxis among haematology and infectious disease clinicians across Australia and New Zealand, and their alignment with existing consensus guidelines for the use of antifungal agents in the haematology/oncology setting (published 2008). Surveyed clinicians largely followed the current recommendations for prophylaxis in the setting of induction chemotherapy for acute myeloid leukaemia, as well as autologous and low-risk allogeneic haemopoietic stem cell transplantation ( HSCT). In keeping with guideline recommendations, posaconazole was the agent used by most centres for high-risk allogeneic HSCT. However, its routine continuation for 75-100 days post-transplantation without de-escalation suggested use beyond those indications described in the 2008 guidelines, namely pre-engraftment neutropenia and graft-versus-host disease. Variations in practice were observed in other settings, such as acute lymphoblastic leukaemia and myelodysplastic syndrome, reflecting the general lack of evidence for antifungal prophylaxis in these patient populations and changing perceptions of risk. With regard to the availability of testing in cases of suspected breakthrough IFD, 40% of centres did not have access to investigative bronchoscopy within 48 h of referral, and results of Aspergillus galactomannan ( GM), fungal polymerase chain reaction and therapeutic drug monitoring ( TDM) were not available within 48 h in 83%, 90% and 85% of centres respectively. The survey's findings will influence the recommendations provided in the updated 2014 consensus guidelines for the use of antifungal agents in the haematology/oncology setting. [ABSTRACT FROM AUTHOR]

The non-canonical Wnt pathway, a regulator of cellular motility and morphology, is increasingly implicated in cancer metastasis. In a quantitative PCR array analysis of 84 Wnt pathway associated genes, both non-canonical and canonical pathways were activated in primary and metastatic tumors relative to normal prostate. Expression of the Wnt target gene PITX2 in a prostate cancer (PCa) bone metastasis was strikingly elevated over normal prostate (over 2,000-fold) and primary prostate cancer (over 200-fold). The elevation of PITX2 protein was also evident on tissue microarrays, with strong PITX2 immunostaining in PCa skeletal and, to a lesser degree, soft tissue metastases. PITX2 is associated with cell migration during normal tissue morphogenesis. In our studies, overexpression of individual PITX2A/B/C isoforms stimulated PC-3 PCa cell motility, with the PITX2A isoform imparting a specific motility advantage in the presence of non-canonical Wnt5a stimulation. Furthermore, PITX2 specific shRNA inhibited PC-3 cell migration toward bone cell derived chemoattractant. These experimental results support a pivotal role of PITX2A and non-canonical Wnt signaling in enhancement of PCa cell motility, suggest PITX2 involvement in homing of PCa to the skeleton, and are consistent with a role for PITX2 in PCa metastasis to soft and bone tissues. Our findings, which significantly expand previous evidence that PITX2 is associated with risk of PCa biochemical recurrence, indicate that variation in PITX2 expression accompanies and may promote prostate tumor progression and metastasis. [ABSTRACT FROM AUTHOR]

Summary: Background: Empirical treatment with antifungal drugs is often used in haematology patients at high risk of invasive aspergillosis. We compared a standard diagnostic strategy (culture and histology) with a rapid biomarker-based diagnostic strategy (aspergillus galactomannan and PCR) for directing the use of antifungal treatment in this group of patients. Methods: In this open-label, parallel-group, randomised controlled trial, eligible patients were adults undergoing allogeneic stem-cell transplantation or chemotherapy for acute leukaemia, with no history of invasive fungal disease. Enrolled patients were randomly assigned (1:1) by a computer-generated schedule to follow either a standard diagnostic strategy (based on culture and histology) or a biomarker-based diagnostic strategy (aspergillus galactomannan and PCR) to direct treatment with antifungal drugs. Patients, were followed up for 26 weeks or until death. Masking of the use of different diagnostic tests was not possible for patients, treating physicians, or investigators. The primary endpoint was empirical treatment with antifungal drugs in the 26 weeks after enrolment (for the biomarker-based diagnostic strategy, a single postive galactomannan or PCR result was deemed insufficient to confirm invasive aspergillosis, so treatment in this context was classified as empirical). This outcome was assessed by an independent data review committee from which the study allocations were masked. Analyses were by intention to treat and included all enrolled patients. This study is registered with ClinicalTrial.gov, number NCT00163722. Findings: 240 eligible patients were recruited from six Australian centres between Sept 30, 2005, and Nov 19, 2009. 122 were assigned the standard diagnostic strategy and 118 the biomarker-based diagnostic strategy. 39 patients (32%) in the standard diagnosis group and 18 (15%) in the biomarker diagnosis group received empirical antifungal treatment (difference 17%, 95% CI 4–26; p=0·002). The numbers of patients who had hepatotoxic and nephrotoxic effects did not differ significantly between the standard diagnosis and biomarker diagnosis groups (hepatotoxic effects: 21 [17%] vs 12 [10%], p=0·11; nephrotoxic effects: 52 [43%] vs 60 [51%], p=0·20). Interpretation: Use of aspergillus galactomannan and PCR to direct treatment reduced use of empirical antifungal treatment. This approach is an effective strategy for the management of invasive aspergillosis in high-risk haematology patients. Funding: Australian National Health and Medical Research Council, Cancer Council New South Wales, Pfizer, Merck, Gilead Sciences. [ABSTRACT FROM AUTHOR]

Although isolated cytopenias are relatively common in human immunodeficiency virus ( HIV), the incidence of aplastic anaemia is extremely rare. We report here the first case of a HIV-infected patient who developed severe idiopathic aplastic anaemia, and who was safely and effectively treated with anti-thymocyte globulin and cyclosporin. We briefly review immune-mediated cytopenias in HIV, including their frequency, pathophysiology and management strategies. [ABSTRACT FROM AUTHOR]

Invasive fungal infections (IFI) are a significant cause of morbidity and mortality in the immunocompromised. The traditional diagnostic methods of culture and histological examination lack sensitivity and often only make a diagnosis late when the fungal burden is high, reducing the chances of cure even with the availability of new more potent and less toxic antifungal agents. New non-culture-based serological and PCR assays have been developed. These appear more sensitive and are able to make an earlier diagnosis as compared with traditional diagnostic methods. Early diagnosis is central to reducing IFI-related morbidity and mortality. This review describes the diagnostic potential of the new serological and PCR assays and outlines how these assays have been incorporated into algorithms to improve the management of IFI. [ABSTRACT FROM AUTHOR]

The study explored the relationship between self and informant reports of emotional problems in a forensic intellectual disability sample. The Emotional Problems Scales (EPS) (Prout & Strohmer, 1991), which comprises a Self Report Inventory (EPS-SRI) and an informant Behaviour Rating Scale (EPS-BRS), was routinely administered to 30 individuals with intellectual disability in a secure forensic setting, as part of a standard clinical assessment procedure. It was hypothesised that there would be a moderate relationship between corresponding scores on the EPS-SRI and EPS-BRS. However, there were no significant relationships between corresponding scales of the EPS-SRI and EPS-BRS, apart from the EPS-SRI and EPS-BRS scales measuring anxiety (r = .376, p<.05). The results continued to be non-significant, even when positive impression management was controlled for. The findings suggest little relationship between self and informant ratings in a forensic intellectual disability sample, and therefore support the need to gather information from multiple sources when assessing such individuals. [ABSTRACT FROM AUTHOR]

Background Despite an increasing knowledge base concerning the assessment of emotional and behavioural problems in people with intellectual disabilities (ID), relatively little research has examined such problems in offenders with ID. Methods The study assessed 172 male offenders with ID in three service settings (high, medium-low security and community) using the Behaviour Rating Scale of the Emotional Problem Scales (EPS), with the aim of assessing differences in Externalizing and Internalizing Behaviour Problems. Results Normative information is presented on the Behaviour Rating Scale of the EPS across three levels of forensic ID care. It was found that offenders in higher secure care scored higher on sub-scales reflecting physical aggression than those in lower secure care. However, there was no difference in terms of other Externalizing Behaviour Problems, such as verbal aggression, non-compliance or hyperactivity. In addition, those offenders in higher secure care scored significantly higher on all Internalizing Behaviour Problems sub-scales, including anxiety, depression and low self-esteem. Conclusions Implications for research and clinical pratice are discussed, including the utility of the EPS as a measure of clinical need and treatment outcome. [ABSTRACT FROM AUTHOR]

Background Among mainstream offenders, the severe personality disorder of psychopathy has considerable importance as a construct. The disorder has long been associated with failure to make treatment progress. Previous work has identified that psychopathy as a disorder occurs in samples of offenders with intellectual disability (ID), and suggests that the Psychopathy Checklist - Revised (PCL-R: Hare, 1991, 2003) as a measure of the disorder has adequate reliability and validity (Morrissey et al., 2005). The present study aimed to compare the predictive power of the PCL-R in relation to treatment progress with a more general assessment of violence risk, the HCR-20 (Webster, Douglas, Eaves, & Hart, 1997). Method A sample of 73 residents in a high security intellectual disability service, who had previously been assessed using the PCL-R and the HCR-20, were followed up at 2 years post-assessment, and their outcome determined in terms of two distinct dichotomous variables reflecting definite positive treatment progress and definite negative treatment progress respectively. Results In line with predictions, the PCL-R Total score and Factor 1 score (Interpersonal and Affective aspects of psychopathy) and the HCR-20 Total score were significantly inversely associated with a positive move from high to medium security hospital conditions within 2 years of assessment. However against prediction, the PCL-R Total score had incremental validity over the HCR-20. The PCL-R Total and Factor 1, but not the HCR-20 Total score, were also significantly associated with negative treatment progress in terms of a move to more restricted treatment conditions. Conclusion Psychopathy, and in particular its interpersonal and affective manifestations, is a construct which appears to be associated with indirect measures of treatment progress in this high security ID group. However, caution should be applied in the use of a construct with potentially negative connotations in an already devalued population. [ABSTRACT FROM AUTHOR]

Soil column studies were used to evaluate petroleum hydrocarbon (PHC) remediation in soils from Kwajalein Atoll. Treatments included controls, and combinations of water, air, nutrients, and bioaugmentation with indigenous microbes (W, A, N, and M, respectively). Microbial colony forming units (CFU) decreased in the control columns and in treatments without air. Treatments including W + A + N and W + A + N + M exhibited increased CFU. One third of the PHC was removed by water and another third was removed by W + A + N and W + A + N + M treatments. Bioaugmentation with indigenous PHC degraders did not enhance bioremediation. Potential for bioremediation was demonstrated by air, water, and nutrient amendments. [ABSTRACT FROM AUTHOR]